Oral administration of anthocyanins, anthocyanidins, and their metabolites for the treatment of inflammation in an inflammed joint

Abstract

The invention provides methods of reducing inflammation and improving the catabolic/anabolic state to promote healing of the cartilage in a joint by providing an oral dosage of either an anthocyanin or an anthocyanidin or their metabolites or a combination thereof. The treatment can occur before surgery, injury or inflammation occurs as a prophylactic treatment and/or can continue during or after the surgery, injury or inflammation has begun.

1 . A method of decreasing inflammation of a joint in a mammalian subject, the method comprising:
 orally administering to the subject a composition comprising an active ingredient selected from the group consisting of ProC3G™, cyanidin-3-glucoside (C3G) or protocatechuic acid (PCA) or a combination thereof,   wherein said composition has the effect of decreasing levels of MMP1, TFG-beta, and MMP13 in the synovial fluid of the joint and increasing the levels of TIMP-1, VEGF, IL-10 and Il-4 in the synovial fluid of the joint to cause a reduction of inflammation in the joint.   
     
     
         2 . The method of  claim 2  wherein the inflammation in the joint is due to an injury or trauma to the joint or due to arthritis of the joint or due to inflammatory arthritis. 
     
     
         3 . The method of  claim 1  wherein the oral administration comprises administering a daily dose for at least 6 weeks of a dose of 0.177 millimoles per kg body weight. 
     
     
         4 . The method of  claim 1  wherein the oral administration comprises administering a daily dose for at least 10 weeks of a dose of 0.177 millimoles per kg body weight. 
     
     
         5 . The method of  claim 1  wherein the oral administration comprises administering a daily dose for at least 4 weeks of a dose of 0.177 millimoles per kg body weight, starting at day 42 after the injury. 
     
     
         6 . A method of improving the catabolic/anabolic state of an inflamed joint in a mammalian subject, the method comprising:
 orally administering to the subject a composition comprising an active ingredient selected from the group consisting of ProC3G™, cyanidin-3-glucoside (C3G) or protocatechuic acid (PCA) or a combination thereof,   wherein said improved catabolic/anabolic state is brought about by a process selected from the group consisting of reduction of levels of MMP3, MMP-1, MMP13, IL-1B, TGF-beta, TNF-alpha, ADAMTS-5, in synovial fluid or synovium; and/or an increase of levels of IGF-1, lubricin, TIMP-1, VEGF, Il-10, IL-4, collagen II and/or aggrecan in synovial fluid or synovium of the inflamed joint.   
     
     
         7 . The method of  claim 1  wherein the MMP 3 levels are reduced in the synovial fluid, synovium and cartilage of the inflamed joint. 
     
     
         8 . The method of  claim 1  wherein IGF-1 levels or gene expression is increased in the synovium of the inflamed joint. 
     
     
         9 . The method of  claim 1  wherein Il-1B levels are decreased in synovial fluid and synovium of the inflamed joint. 
     
     
         10 . The method of  claim 1  wherein lubricin levels are increased in the synovium of the inflamed joint. 
     
     
         11 . The method of  claim 1  wherein the levels of TNF-alpha are decreased in the synovium of the inflamed joint. 
     
     
         12 . The method of  claim 1  wherein the levels of ADAMTS-5 are decreased in the synovial fluid and gene expression is decreased in the synovium of the inflamed joint. 
     
     
         15 . A method of decreasing the numbers of macrophages, lymphocytes and polymorphonuclear leukocytes in synovial fluid of an inflamed joint by orally administering to a subject a composition comprising an active ingredient selected from the group consisting of ProC3G™ cyanidin-3-glucoside (C3G) or protocatechuic acid (PCA) or a combination thereof. 
     
     
         16 . A method of decreasing inflammation of a joint in a mammalian subject, the method comprising:
 orally administering to the subject a composition comprising an active ingredient selected from the group consisting of an anthocyanin or a metabolite thereof, or an anthocyanidin or a metabolite thereof or a combination thereof,   wherein said composition has the effect of decreasing levels of MMP1, TFG-beta, and MMP13 in the synovial fluid of the joint and increasing the levels of TIMP-1, VEGF, IL-10 and Il-4 in the synovial fluid of the joint to cause a reduction of inflammation in the joint.   
     
     
         17 . A method treating an injured or arthritic joint by promoting healing of the cartilage of the joint in a mammalian subject, the method comprising:
 orally administering to the subject a composition comprising an active ingredient selected from the group consisting of ProC3G™, cyanidin-3-glucoside (C3G) or protocatechuic acid (PCA) or a combination thereof,   wherein said composition has the effect of increasing in the cartilage of the injured or arthritic joint expression levels of lubricin, aggrecan and collagen II to promote healing and to treat the injured or arthritic joint.   
     
     
         19 . A method of decreasing levels of C reactive protein (CRP) in the plasma in a subject having an inflamed or injured joint, the method comprising orally administering to the subject a composition comprising an active ingredient selected from the group consisting of ProC3G™ cyanidin-3-glucoside (C3G) or protocatechuic acid (PCA) or a combination thereof,
 wherein said administration has the effect of decreasing levels of CRP in the plasma of the subject. 
 
     
     
         20 . A formulation for oral administration to a patient for reducing inflammation in an injured or arthritic joint, the formulation comprising an active ingredient selected from the group consisting of an anthocyanin or one of its metabolites, an anthocyanidin or one its metabolites, C3G, and PCA. 
     
     
         21 . A method of providing a prophylactic treatment to a subject to reduce inflammation, wherein the formulation of  claim 20  is provided to the subject in advance of a surgery to the joint. 
     
     
         22 . The method of  claim 21  further comprising providing to the subject the formulation after the surgery. 
     
     
         23 . A method of providing a therapeutic treatment to a subject to reduce inflammation after surgery, wherein the formulation of  claim 20  is provided to the subject after surgery to the joint.